The present invention relates to a liquid dispensing system for forming and dispensing droplets of a liquid sample.
Many chemical, biomedical, bioscience and pharmaceutical industries require chemical operations, such as reactions, separations and subsequent detection steps, to be performed on samples. It is generally desirable to introduce these samples into a sample handling system, such as a microfluidic system capable of handling and analyzing chemical and biological specimens, quickly, efficiently and in a highly controllable manner.
Many methods have been described for the interfacing of fluids, e.g., samples, analytes, reagents, precursors for synthesis and buffers, towards, within or between microfluidic systems. Generally, introduction of a liquid sample to a microfluidic system is accomplished through sample channels or sample wells. To introduce a liquid sample to the microfluidic system, a capillary tube may be provided, which dispenses a liquid sample to a sample well, sample channel or other sample introduction port. A significant drawback of using a capillary tube concerns the low injection efficiency inherent to capillary tubes, that is, the ratio between the volume of liquid required for a particular chemical operation in a part of the microfluidic system, and the total volume of liquid required for the introductory operation. Moreover, it is generally difficult to control the precise volume of dispensed sample using capillary tubes. Furthermore, capillary tubes are subject to contamination, because the same port used to fill the tube is also used to eject the liquid sample.
U.S. Pat. No. 6,101,946 of Martinsky describes a pin-based system for printing microarrays of biochemical substances. The microarray printing system comprises a printing pin having a sample channel and a flat tip. The pin applies a biochemical substance by filling the sample channel and subsequently directly contacting a printing substrate, to deliver the sample from the sample channel to the printing substrate. A drawback of the pin-based system described in the ""946 patent concerns the ability to control the amount of delivered sample. The pin-based system is subject to contamination and breakage, because it requires direct contact between the pin tip and the printing substrate. Another drawback concerns the difficulty of precisely positioning the tip of the pin to provide sufficient contact to result in delivery of a sample.
U.S. Pat. No. 6,110,426 of Shalon et al., the contents of which are herein incorporated by reference, describes a capillary dispenser for forming microarrays of biological samples. The capillary dispenser comprises an elongate open capillary channel adapted to hold a liquid sample. The channel is formed by a pair of spaced-apart, coextensive, elongate members, which are tapered toward one another and converge at a tip region at the lower end of the channel. The elongate members are fixed relative to each other and the capillary channel is limited to a fixed volume. Furthermore, it is difficult to control the amount of sample that is acquired and dispensed from the capillary dispenser of the ""246 patent.
The present invention provides a droplet dispensing system which forms and dispenses droplets of a liquid sample on demand. The droplet dispensing system comprises a holder and one or more dispensing pins. Each dispensing pin has a tip for forming and ejecting droplets of a liquid sample from a supply of liquid sample stored in the tip. The tip of each dispensing pin includes a droplet ejection nozzle for controllably and selectively ejecting a droplet of liquid from the tip of the dispensing pin. Each dispensing pin tip includes a sample chamber in fluid communication with the ejection nozzle for holding a supply of a liquid sample. The tip further includes a filling channel in fluid communication with the sample chamber for filling the tip with a predetermined volume of liquid sample from a reservoir. An actuator is located on the tip adjacent to the ejection nozzle and communicates with the sample chamber. The droplet dispensing system forms and ejects droplets through the ejection nozzle by activating the actuator.
A method of manufacturing a dispensing system is also provided. According to the illustrative embodiment, the droplet dispensing system is fabricated from a silicon wafer. A photolithography process is utilized to etch the filling channel, sample chamber and ejection nozzle in the tip of a dispensing pin. A suitable actuator is attached to the tip to provide for formation and ejection of droplets from the ejection nozzle.
The droplet dispensing system provides fast and flexible filling of a predetermined amount of liquid sample in the dispensing system via the tip of a dispensing pin. The droplet dispensing system provides efficient and rapid dispensing of the liquid sample from the tip of a dispensing pin in the form of droplets having a precisely controlled volume. The droplet dispensing system enhances liquid sample application by improving efficiency, speed and controllability, while reducing waste and contamination.
According to one aspect a droplet dispensing system comprising a dispensing pin is provided. The sample dispensing system comprises a dispensing pin having a tip. The tip includes a sample chamber, a sample filling channel formed in the tip and in fluid communication with the sample chamber for loading a liquid sample into the sample chamber a droplet ejection nozzle in fluid communication with the sample chamber for ejecting a droplet of the liquid sample from the sample chamber and an actuator located adjacent to the sample chamber for forming the droplet.
According to another aspect, a droplet dispensing system comprises two interacting pins is provided. The two-pin droplet dispensing system comprises a first pin and a dispensing pin positioned in proximity to each other to form a filling channel therebetween. The dispensing pin has a tip further comprising a sample chamber located in fluid communication with the sample filling channel, an ejection nozzle for ejecting a droplet from the sample chamber and an actuator for triggering formation and ejection of a droplet from the ejection nozzle.
According to yet another aspect, a method of dispensing a liquid sample is provided. The method of dispensing a liquid sample comprises providing a droplet dispensing system comprising a pin having a tip including filling channel for filling the tip with a predetermined volume of liquid sample, a sample chamber, an ejection nozzle and an actuator for effecting formation of a droplet. The method further comprises the step of activating the actuator to produce a droplet of liquid sample at the sample ejection nozzle.
According to another aspect, a liquid sample dispensing system, comprising a holder and an array of dispensing pins connected to the holder is provided. Each dispensing pin in the array has a tip and a sample chamber formed in the tip for holding a predetermined volume of sample, a sample filling channel formed in the tip and in fluid communication with the sample chamber for loading a liquid sample into the sample chamber and a droplet ejection nozzle in fluid communication with the sample chamber for ejecting a droplet of the liquid sample from the sample chamber. The liquid sample dispensing system further includes an actuator coupled to the sample chamber of one or more of the dispensing pins for forming one or more droplets upon activation of the actuator.